Quantifying possible routes for SpnF-catalyzed formal Diels-Alder cycloaddition
The Diels-Alder reaction is a cornerstone of modern organic synthesis. Despite this, it remains essentially inaccessible to biosynthetic approaches. Only a few natural enzymes catalyze even a formal [4+2] cycloaddition, and it remains uncertain if any of them proceed via the Diels-Alder mechanism. In this study, we focus on the [4+2] cycloaddition step in the biosynthesis of spinosyn A, a reaction catalyzed by SpnF enzyme—one of the most promising “true Diels-Alderase” candidates. The four currently proposed mechanisms (including the Diels-Alder one) for this reaction in water (as a first-order approximation of the enzymatic reaction) are evaluated by an exhaustive quantum mechanical search for possible transition states (728 were found in total). We find that the line between the recently proposed bis-pericyclic [J. Am. Chem. Soc. 2016, 138 (11), 3631] and Diels-Alder routes is blurred, and favorable transition states of both types may coexist. Application of the Curtin-Hammett principle, however, reveals that the bis-pericyclic mechanism accounts for ≈83% of the reaction flow in water, while the classical Diels-Alder mechanism contributes only ≈17%. The current findings provide a route for modeling this reaction inside the SpnF active site and inferring the catalytic architecture of possible Diels-Alderases.
Referential choice between various referential expressions, such as de-scriptions, proper names, and pronouns, depends on a variety of factors. We present recent results of our modeling study into referential choice, based on the RefRhet corpus. The account of additional factors and the employment of mixed machine learning techniques enabled an improvement of referential choice prediction. This applies both to the two-way choice between full NP and pronoun and to the threeway choice “descriptive full NP vs. proper name vs. pronoun”. We have demonstrated that the great majority of the factors taken into account are significant for modeling the referential choice.
This paper is dedicated to the comparative analysis of existential ontological concepts of M. Heidegger and H. Plessner from the perspective of philosophical anthropology. Unlike Heidegger, whose doctrine of human existence required the analysis of a priori structures of existence to precede the disclosure of the sense of being, Plessner refutes the existential ontological substantiation of the whole world-view in the pre-empirical anthropology as in the doctrine of «being-consciousness». According to Plessner, the philosophy of man is impossible without the philosophy of nature, as far as the human mode of existence can be perceived only as a mode of being of a natural entity. Therefore the subject of philosophy should not be the theoretical, but the «living», or natural, existence.
We now know that the Iron Curtain was not an impenetrable wall but, rather, a porous imaginary boundary through which people, ideas, and goods could travel. This volume is a fresh attempt to look across two blocs to examine variations, similarities, and connections between what we used to call East and West. As editors Astrid Mignon Kirchhof and John R. McNeill explain in the introduction, the volume aims to challenge a traditional question about the East-West divide. It focuses on the environment and its connections to politics, culture, and society.
The book about nature of Moscow region/
Plein-air in additional education studio organization is being discussed in the article. As a part of estetic students' education, open-air represents drawing and painting outside in open-air. Purpose of open-air working is to fasten and broaden knowledge and experience received during academic year, to develop abilities of its creative application in open space natural illumination conditions. Different activities are being described: drawing (doodle, sketch, long-tirmed drawing) and painting (short-termed and long-termed etude).
One of the key advances in genome assembly that has led to a significant improvement in contig lengths has been improved algorithms for utilization of paired reads (mate-pairs). While in most assemblers, mate-pair information is used in a post-processing step, the recently proposed Paired de Bruijn Graph (PDBG) approach incorporates the mate-pair information directly in the assembly graph structure. However, the PDBG approach faces difficulties when the variation in the insert sizes is high. To address this problem, we first transform mate-pairs into edge-pair histograms that allow one to better estimate the distance between edges in the assembly graph that represent regions linked by multiple mate-pairs. Further, we combine the ideas of mate-pair transformation and PDBGs to construct new data structures for genome assembly: pathsets and pathset graphs.
Papers about natural protection territories
Many environmental stimuli present a quasi-rhythmic structure at different timescales that the brain needs to decompose and integrate. Cortical oscillations have been proposed as instruments of sensory de-multiplexing, i.e., the parallel processing of different frequency streams in sensory signals. Yet their causal role in such a process has never been demonstrated. Here, we used a neural microcircuit model to address whether coupled theta–gamma oscillations, as observed in human auditory cortex, could underpin the multiscale sensory analysis of speech. We show that, in continuous speech, theta oscillations can flexibly track the syllabic rhythm and temporally organize the phoneme-level response of gamma neurons into a code that enables syllable identification. The tracking of slow speech fluctuations by theta oscillations, and its coupling to gamma-spiking activity both appeared as critical features for accurate speech encoding. These results demonstrate that cortical oscillations can be a key instrument of speech de-multiplexing, parsing, and encoding.
Neuronal nicotinic acetylcholine receptors (NNRs) of the α7 subtype have been shown to contribute to the release of dopamine in the nucleus accumbens. The site of action and the underlying mechanism, however, are unclear. Here we applied a circuit modeling approach, supported by electrochemical in vivo recordings, to clarify this issue. Modeling revealed two potential mechanisms for the drop in accumbal dopamine efflux evoked by the selective α7 partial agonist TC-7020. TC-7020 could desensitize α7 NNRs located predominantly on dopamine neurons or glutamatergic afferents to them or, alternatively, activate α7 NNRs located on the glutamatergic afferents to GABAergic interneurons in the ventral tegmental area. Only the model based on desensitization, however, was able to explain the neutralizing effect of coapplied PNU-120596, a positive allosteric modulator. According to our results, the most likely sites of action are the preterminal α7 NNRs controlling glutamate release from cortical afferents to the nucleus accumbens. These findings offer a rationale for the further investigation of α7 NNR agonists as therapy for diseases associated with enhanced mesolimbic dopaminergic tone, such as schizophrenia and addiction